CANCER

During the twentieth century wealthy countries underwent a transition in mortality from acute, infectious diseases such as pneumonia to chronic diseases such as cancer. By the late twentieth century the lifetime risk of a person receiving a cancer diagnosis in the United States had climbed above one-in-three. The quest for an elusive "cure" for cancer became a policy imperative, and by the first decade of the twenty-first century U.S. government expenditures on cancer research had reached three billion dollars per year. Notwithstanding decades of heavy research funding, advances in long-term survival for many of the common types of cancer have remained insignificant, and critics have charged that research funding has been too narrowly focused.

Etiologies

The ancient Greeks and Romans understood cancer and other diseases in terms of the bodily humors of phlegm, blood, black bile, and yellow bile (Rather 1978). When the humors were out of balance, such as an excess of black bile in the case of cancer, a disease could erupt. Similar humoral approaches characterized other Old World medical systems, such as the traditional medicines of east and south Asia. Although the rise of scientific biology displaced humoral thinking from the medical sciences, humoral approaches to disease can still be found in some complementary and alternative medicine (CAM) approaches to cancer, such as macrobiotic, Ayurvedic, and other traditional Asian medical systems, as well as in general notions of rebalancing the body. Ancient physicians also identified diet and trauma as two possible environmental sources of cancer, and those ideas continue to be relevant to thinking on the etiology (causes) of cancer in the early-twenty-first century.

By the beginning of the twentieth century medical researchers were pursuing diverse approaches to cancer etiology. In the wake of the bacteriological revolution, many researchers thought that cancer was an infectious, bacterial disease. Although bacterial theories and therapies were on the wane by the 1920s, throughout the twentieth century a marginal network of researchers kept the approach alive, and they developed dietary and vaccine-based therapies (Hess 1997). At the end of the twentieth century, bacteria were gaining some general recognition as a risk factor for digestive tract cancers. Viral oncology, which had a peak of popularity during the 1960s, had also won general acceptance for viruses as the cause of some human and animal cancers.

At a popular level, laypeople in early-twentieth-century Western countries frequently believed that trauma was a significant cause of cancer (Clow 2001), and the belief is still widespread in some countries. The medical profession recognized a related risk factor of tissue irritation from sources such as tobacco or childbirth. The interest in tissue irritation gradually developed into research programs on chemical carcinogenesis. In the eighteenth century the relationship between creosote tar and scrotal cancer in chimney sweeps had been identified. By the end of the twentieth century, a wide range of chemicals, as well as some forms of electromagnetic radiation, were acknowledged as risk factors, including especially the carcinogens in cigarette smoke.

At the beginning of the twentieth century, some medical researchers also drew attention to the role of internal biological processes in cancer etiology. One theory assumed that embryonic cells remained embedded in differentiated tissues and that they could develop into cancer under some conditions. The theory did not win widespread acceptance, but therapies based on enzymes and other dietary modifications continued as part of the field of CAM cancer care. Furthermore the theory drew attention to the role of growth hormones in cancer, which became part of mainstream cancer research. By the middle decades of the twentieth century, research programs were also emerging on the role of sex hormones in some cancers.

Another development during the twentieth century was research on inherited susceptibility to cancer, which developed from longstanding beliefs about heredity and cancer. Animal experiments in the early decades of the twentieth century confirmed the role of heredity, and by the late-twentieth century it became clear that some types of inherited gene variations (alleles) carried very high risk for some types of cancer, such as the BRCA1 and BRCA2 genes for breast cancer. However, epidemiologists at the end of the twentieth century generally believed that heredity explained only a minor percentage of the variation in the aggregate incidence of cancer and in its growth in incidence.

The development of molecular biology in the second half of the twentieth century allowed a synthesis of various risk factors (for example viruses, chemical carcinogens, radiation) at the molecular level of genetic damage and the expression of genes related to cancer (oncogenes and tumor suppressor genes). However, heredity as a risk factor needs to be distinguished from the understanding of carcinogenesis at a molecular level. Epidemiologists have increasingly given priority to environmental and lifestyle factors, of which diet and exposure to carcinogenic chemicals are generally seen as the central risk factors. In the early-twenty-first century, other recognized risk factors include reproductive behavior, obesity, viral infection, and excessive exposure to sunlight.

Ethics in the Clinical Setting

Most discussions of ethics and cancer focus on the doctor-patient relationship and the various types of ethical problems that emerge in cancer diagnosis and treatment (Angelos 1999). A key issue involves the communication of information to the patient. In some countries physicians have historically informed family members of the diagnosis but have concealed the diagnosis from the patient, even if the patient asks for the information. The practice appears to be changing, but other questions remain. For example, should a physician inform the patient of the diagnosis and/or prognosis, even if the patient asks not to be informed? Likewise should a clinician volunteer statistical information about prognosis even when only more general information is requested?

A related but in a sense inverted problem involves the disclosure to kin of a known genetic mutation that is related to cancer, such as the BRCA1/2 mutation. Patients who undergo such testing often do not expect to benefit personally from it, but they hope that the information will be helpful to kin. As a result, questions have been raised about informed consent regarding the autonomy of the patients who undergo testing, who may feel compelled by responsibility toward kin as a reason for undertaking the testing, as well as the autonomy of kin, who may not want to know such information or may fear genetic discrimination (Hallowell et al. 2003).

A second issue in the doctor-patient relationship involves the ethics of physician reactions to decisions by patients to withdraw from treatment. Sometimes patients decide that the side effects of conventional treatments, such as chemotherapy, are too severe in comparison with the potential benefits (long-term remission) for their particular type of cancer. Patients may combine the decision to withdraw from treatment with a decision to opt for a CAM treatment, but sometimes they simply forego chemotherapy for reasons other than pursuing a successful treatment. For example, patients may decide that there is no hope for recovery and that they are ready to die, or they may feel healthy and may want to work until they no longer can. However oncologists may not recognize nonmedical reasons as good reasons for refusing treatment, or they may reject the patient's assessment of the relative risks and benefits of various options, and consequently a communication gap may emerge when oncologists refuse to continue to monitor patients who refuse treatment (Huijer and Leeuwen 2000).

When parents make similar decisions for children, the cases can end in bitter conflicts. In some cases doctors have called in state agencies to take children away from their parents and forcibly deliver conventional therapies. Presumably some calculation of the benefits and risks of both the proposed conventional therapy (including no treatment) and the alternative treatment option (including no treatment) pursued by the parents inform decisions about whether to support the parents or take their child away. As a result, in some cases doctors may support the parents' decision. For example, a child was diagnosed with a type of brain tumor for which conventional therapies offered no possibility of cure. The parents decided to try antineoplastons, an experimental therapy that had only limited supporting evidence at the time but held some risk associated with the insertion of an intravenous catheter. In this case the doctors and hospital opted to insert the catheter and follow the patient, but they also informed the parents of their skepticism that the therapy would be beneficial (Jackson 1994).

Ethics and Research Funding

Ethical issues have also emerged around the politics of funding. One key area has been research funding on chemical carcinogenesis. For years, evidence that smoking is a substantial risk factor for lung cancer (as well as some other types of cancer) was suppressed, and epidemiologists who sought funds for and produced evidence on the role of smoking faced a long battle for recognition. In the early-twenty-first century a younger generation of epidemiologists faces a similar battle to gain acceptance for claims that military and industrial pollution is a major risk factor (Davis and Webster 2002). Historically researchers who have attempted to document risks from industrial pollutants such as ionizing radiation have faced suppression, and industry support groups also have produced scientific dissensus by funding studies that questioned the risks associated with industrial pollutants (Proctor 1995).

In addition to the politics of funding for research on etiology, ethical issues also have emerged around funding choices for research that evaluates or develops therapies. In the early twentieth century surgery was the only mainstream therapy for cancer, but radium-based therapies gained currency by the 1920s, and chemotherapy emerged after World War II. Surgeons and physicians who owned radium or advocated chemotherapy actively opposed the vaccine-oriented therapies developed by researchers who adopted immunological or biological approaches (Hess 1997). Similar suppression has been documented for nutritional therapies and a range of other CAM approaches to cancer (Moss 1995).

As cancer treatment developed during the twentieth century, medical subspecialties and cancer-related treatment industries opposed radical changes in treatment that threatened to undercut the profits of surgery, radiation therapy, and patented drugs. Although biological/immunological therapies for cancer (such as the use of interleukins and drugs that block the formation of blood vessels) are gaining ground in the early-twenty-first century, those developments take place through the mechanism of patented drug development. Researchers who investigate therapies that rely on unpatented products derived from plant or animal substances have been unable to obtain the level of private sector investment that is necessary to become competitors in the field of cancer therapy, which after the early 1960s involved a very costly drug approval process. As a result, a wide range of potentially lifesaving therapies has remained underinvestigated. Public funding agencies in the United States and other countries that could have stepped in to provide research funding for orphaned, unpatented therapies did not do so until the late-twentieth century, and even then the funding remained very minimal. (The term "orphaned" refers to therapies that lack sufficient research funding to be brought to market, because private firms cannot recuperate research costs in future sales due to lack of patentability or size of market.)

Another way in which research on unpatented products can hit a dead end is due to the way that the ethics of clinical trials has developed. Ethicists have argued in favor of equipoise, that is, the condition that study and treatment arms in a clinical trial have equal risk/benefit profiles. As a result, in cancer research placebo controls are rarely used; instead an experimental treatment is compared to the treatment standard. Frequently the experimental treatment is the standard treatment plus an additional drug. The standard of equipoise protects patients with life-threatening diseases from research that would put them at risk of receiving completely inefficacious treatment. However because funding is absent to generate preliminary human data, unpatented therapies can be locked in a limbo that prevents head-to-head testing against standard therapies. In this way ethical considerations at one level (patient rights) can negatively impact ethical considerations at another level (investigation of orphaned or unpatented therapies).

In short, significant ethical issues remain unaddressed regarding research funding for both etiology and treatment. Industrial interests external to cancer research and treatment, such as industries that generate significant pollution with suspected carcinogens, have opposed research that might lead to costly changes in materials or production processes. Likewise industrial interests internal to cancer research and treatment, such as medical subspecialties and the pharmaceutical/biotechnology industries, have opposed research that might open the door to competition from unpatented products. After decades of publicly supported research that have followed President Nixon's declaration of the war on cancer in 1971, for many patients therapeutic options remain limited and long-term prognosis remains dismal.

DAVID HESS

SEE ALSO Death and Dying;Health and Disease;Medical Ethics.

BIBLIOGRAPHY

Angelos, Peter. (1999). Ethical Issues in Cancer Patient Care. Dordrecht, The Netherlands: Kluwer. Good survey of the bedside ethical dimensions of conventional cancer care.

Clow, Barbara. (2001). Negotiating Disease. Montreal McGill-Queen's University Press. Survey of popular and academic understandings of cancer etiology in the twentieth-century.

Davis, Devra Lee, and Pamela Webster. (2002). "Epidemiology and Science: The Social Context of Science." Annals of the American Academy of Political and Social Science 584(13): 13–34. Example of the younger generation of epidemiologists that is developing the case for environmental etiologies.

Hallowell, Nina; Foster, C.; Eeles, R., et al. (2003). "Balancing Autonomy and Responsibility: The Ethics of Generating and Disclosing Genetic Information. Journal of Medical Ethics 29(2): 74–79. A leading journal for those interested in medical ethics.

Hess, David. (1997). Can Bacteria Cause Cancer? New York: New York University Press. A multidisciplinary analysis of the history of one type of alternative theory and therapy for cancer, analysis of its suppression, evaluation of the evidence, and discussion of policy remedies.

Huijer, Marli, and Evert van Leeuwen. (2000). "Personal Values and Cancer Treatment Refusal." Journal of Medical Ethics 26(5): 358–362.

Jackson, Jennifer. (1994). "Unproven Treatment in Childhood Oncology: How Far Should Pediatricians Co-Operate? Commentary." Journal of Medical Ethics 20: 77–79.

Moss, Ralph. (1995). The Cancer Industry. Brooklyn, NY: Equinox Press. Classic study of the suppression of alternative cancer therapies and researchers.

Proctor, Robert. (1995). Cancer Wars. New York: Basic Books. Review of research controversies surrounding environmental etiologies of cancer.

Rather, L. J. (1978). The Genesis of Cancer: A Study of the History of Ideas. Baltimore, MD: Johns Hopkins University Press. Examples the early theories of cancer.